Navraj S Nagra

Bio: Navraj S Nagra is an academic researcher from University of Oxford. The author has contributed to research in topics: Rotator cuff & Population. The author has an hindex of 9, co-authored 27 publications receiving 277 citations. Previous affiliations of Navraj S Nagra include University of Manchester & British Orthopaedic Association.

One-stage versus two-stage exchange arthroplasty for infected total knee arthroplasty: a systematic review

Abstract: Purpose Infection complicating total knee arthroplasty (TKA) has serious implications. Traditionally the debate on whether one- or two-stage exchange arthroplasty is the optimum management of infected TKA has favoured two-stage procedures; however, a paradigm shift in opinion is emerging. This study aimed to establish whether current evidence supports one-stage revision for managing infected TKA based on reinfection rates and functional outcomes post-surgery.

Mechanical properties of all-suture anchors for rotator cuff repair.

Abstract: Objectives All-suture anchors are increasingly used in rotator cuff repair procedures. Potential benefits include decreased bone damage. However, there is limited published evidence for the relative strength of fixation for all-suture anchors compared with traditional anchors. Materials and Methods A total of four commercially available all-suture anchors, the ‘Y-Knot’ (ConMed), Q-FIX (Smith & Nephew), ICONIX (Stryker) and JuggerKnot (Zimmer Biomet) and a traditional anchor control TWINFIX Ultra PK Suture Anchor (Smith & Nephew) were tested in cadaveric human humeral head rotator cuff repair models (n = 24). This construct underwent cyclic loading applied by a mechanical testing rig (Zwick/Roell). Ultimate load to failure, gap formation at 50, 100, 150 and 200 cycles, and failure mechanism were recorded. Significance was set at p Results Overall, mean maximum tensile strength values were significantly higher for the traditional anchor (181.0 N, standard error (se) 17.6) compared with the all-suture anchors (mean 133.1 N se 16.7) (p = 0.04). The JuggerKnot anchor had greatest displacement at 50, 100 and 150 cycles, and at failure, reaching statistical significance over the control at 100 and 150 cycles (22.6 mm se 2.5 versus 12.5 mm se 0.3; and 29.6 mm se 4.8 versus 17.0 mm se 0.7). Every all-suture anchor tested showed substantial (> 5 mm) displacement between 50 and 100 cycles (6.2 to 14.3). All-suture anchors predominantly failed due to anchor pull-out (95% versus 25% of traditional anchors), whereas a higher proportion of traditional anchors failed secondary to suture breakage. Conclusion We demonstrate decreased failure load, increased total displacement, and variable failure mechanisms in all-suture anchors, compared with traditional anchors designed for rotator cuff repair. These findings will aid the surgeon’s choice of implant, in the context of the clinical scenario. Cite this article: N. S. Nagra, N. Zargar, R. D. J. Smith, A. J. Carr. Mechanical properties of all-suture anchors for rotator cuff repair. Bone Joint Res 2017;6:82–89. DOI: 10.1302/2046-3758.62.BJR-2016-0225.R1

Integrin - dependent mechanotransduction in mechanically stimulated human annulus fibrosus cells: evidence for an alternative mechanotransduction pathway operating with degeneration.

Abstract: Intervertebral disc (IVD) cells derived from degenerate tissue respond aberrantly to mechanical stimuli, potentially due to altered mechanotransduction pathways. Elucidation of the altered, or alternative, mechanotransduction pathways operating with degeneration could yield novel targets for the treatment of IVD disease. Our aim here was to investigate the involvement of RGD-recognising integrins and associated signalling molecules in the response to cyclic tensile strain (CTS) of human annulus fibrosus (AF) cells derived from non-degenerate and degenerate IVDs. AF cells from non-degenerate and degenerate human IVDs were cyclically strained with and without function blocking RGD – peptides with 10% strain, 1.0 Hz for 20 minutes using a Flexercell® strain device. QRT-PCR and Western blotting were performed to analyse gene expression of type I collagen and ADAMTS -4, and phosphorylation of focal adhesion kinase (FAK), respectively. The response to 1.0 Hz CTS differed between the two groups of AF cells, with decreased ADAMTS -4 gene expression and decreased type I collagen gene expression post load in AF cells derived from non-degenerate and degenerate IVDs, respectively. Pre-treatment of non-degenerate AF cells with RGD peptides prevented the CTS-induced decrease in ADAMTS -4 gene expression, but caused an increase in expression at 24 hours, a response not observed in degenerate AF cells where RGD pre-treatment failed to inhibit the mechano-response. In addition, FAK phosphorylation increased in CTS stimulated AF cells derived from non-degenerate, but not degenerate IVDs, with RGD pre-treatment inhibiting the CTS – dependent increase in phosphorylated FAK. Our findings suggest that RGD -integrins are involved in the 1.0 Hz CTS – induced mechano-response observed in AF cells derived from non-degenerate, but not degenerate IVDs. This data supports our previous work, suggesting an alternative mechanotransduction pathway may be operating in degenerate AF cells.

Athletic Population with Spondylolysis: Review of Outcomes following Surgical Repair or Conservative Management.

Abstract: Study Design Narrative review. Objective The study aims to critically review the outcomes associated with the surgical repair or conservative management of spondylolysis in athletes. Methods The English literature listed in MEDLINE/PubMed was reviewed to identify related articles using the term “spondylolysis AND athlete.” The criteria for studies to be included were management of spondylolysis in athletes, English text, and no year, follow-up, or study design restrictions. The references of the retrieved articles were also evaluated. The primary outcome was time to return to sport. This search yielded 180 citations, and 25 publications were included in the review. Results Treatment methods were dichotomized as operative and nonoperative. In the nonoperative group, 390 athletes were included. A combination of bracing with physical therapy and restriction of activities was used. Conservative measures allowed athletes to return to sport in 3.7 months (weighted mean). One hundred seventy-four patients were treated surgically. The most common technique was Buck's, using a compression screw (91/174). All authors reported satisfactory outcomes. Time to return to play was 7.9 months (weighted mean). There were insufficient studies with suitably homogenous subgroups to conduct a meta-analysis. Conclusion There is no gold standard approach for the management of spondylolysis in the athletic population. The existing literature suggests initial therapy should be a course of conservative management with thoracolumbosacral orthosis brace, physiotherapy, and activity modification. If conservative management fails, surgical intervention should be considered. Two-sided clinical studies are needed to determine an optimal pathway for the management of athletes with spondylolysis.

Survival of encapsulated islets: More than a membrane story

Abstract: At present, proven clinical treatments but no cures are available for diabetes, a global epidemic with a huge economic burden. Transplantation of islets of Langerhans by their infusion into vascularized organs is an experimental clinical protocol, the first approach to attain cure. However, it is associated with lifelong use of immunosuppressants. To overcome the need for immunosuppression, islets are encapsulated and separated from the host immune system by a permselective membrane. The lead material for this application is alginate which was tested in many animal models and a few clinical trials. This review discusses all aspects related to the function of transplanted encapsulated islets such as the basic requirements from a permselective membrane (e.g., allowable hydrodynamic radii, implications of the thickness of the membrane and relative electrical charge). Another aspect involves adequate oxygen supply, which is essential for survival/performance of transplanted islets, especially when using large retrievable macro-capsules implanted in poorly oxygenated sites like the subcutis. Notably, islets can survive under low oxygen tension and are physiologically active at > 40 Torr. Surprisingly, when densely crowded, islets are fully functional under hyperoxic pressure of up to 500 Torr (> 300% of atmospheric oxygen tension). The review also addresses an additional category of requirements for optimal performance of transplanted islets, named auxiliary technologies. These include control of inflammation, apoptosis, angiogenesis, and the intra-capsular environment. The review highlights that curing diabetes with a functional bio-artificial pancreas requires optimizing all of these aspects, and that significant advances have already been made in many of them.

Outcome of single-stage versus two-stage exchange for revision knee arthroplasty for chronic periprosthetic infection

Abstract: The gold standard for treating chronic periprosthetic joint infection is still considered to be double-stage exchange revision. The purpose of this review is to analyse the difference in terms of eradication rates and functional outcome after single- and double-stage prosthetic exchange for chronic periprosthetic joint infection around the knee.We reviewed full text articles written in English from 1992 to 2018 reporting the success rates and functional outcomes of either single-stage exchange or double-stage exchange for knee arthroplasty revision performed for chronic infection. In the case of double-stage exchange, particular attention was paid to the type of spacer: articulating or static.In all, 32 articles were analysed: 14 articles for single-stage including 687 patients and 18 articles for double-stage including 1086 patients. The average eradication rate was 87.1% for the one-stage procedure and 84.8% for the two-stage procedure. The functional outcomes were similar in both groups: the average Knee Society Knee Score was 80.0 in the single-stage exchange group and 77.8 in the double-stage exchange. The average range of motion was 91.4° in the single-stage exchange group and 97.8° in the double-stage exchange group.Single-stage exchange appears to be a viable alternative to two -stage exchange in cases of chronic periprosthetic joint infection around the knee, provided there are no contra-indications, producing similar results in terms of eradication rates and functional outcomes, and offering the advantage of a unique surgical procedure, lower morbidity and reduced costs. Cite this article: EFORT Open Rev 2019;4:495-502. DOI: 10.1302/2058-5241.4.190003.

Acidic pH promotes intervertebral disc degeneration: Acid-sensing ion channel -3 as a potential therapeutic target.

Abstract: The aetiology of intervertebral disc (IVD) degeneration remains poorly understood. Painful IVD degeneration is associated with an acidic intradiscal pH but the response of NP cells to this aberrant microenvironmental factor remains to be fully characterised. The aim here was to address the hypothesis that acidic pH, similar to that found in degenerate IVDs, leads to the altered cell/functional phenotype observed during IVD degeneration, and to investigate the involvement of acid-sensing ion channel (ASIC) -3 in the response. Human NP cells were treated with a range of pH, from that of a non-degenerate (pH 7.4 and 7.1) through to mildly degenerate (pH 6.8) and severely degenerate IVD (pH 6.5 and 6.2). Increasing acidity of pH caused a decrease in cell proliferation and viability, a shift towards matrix catabolism and increased expression of proinflammatory cytokines and pain-related factors. Acidic pH resulted in an increase in ASIC-3 expression. Importantly, inhibition of ASIC-3 prevented the acidic pH induced proinflammatory and pain-related phenotype in NP cells. Acidic pH causes a catabolic and degenerate phenotype in NP cells which is inhibited by blocking ASIC-3 activity, suggesting that this may be a useful therapeutic target for treatment of IVD degeneration.